Last updated:
9/06/2023
Years published: 1986, 1987, 1989, 1997, 2002, 2019, 2023
NORD gratefully acknowledges Etienne Leveille, MD, and Helen A. Shih, MD, MS, MPH, Chief, CNS & Eye Services, Department of Radiation Oncology; Medical Director, MGH Proton Therapy Centers, Massachusetts General Hospital, for assistance in the preparation of this report.
Summary
A meningioma is a tumor arising from the meninges, which are membranes covering the brain and spinal cord. Excluding brain metastases from other organs, they are the most common intracranial tumor and are the most common primary brain tumor. They arise more commonly in women and in older individuals and develop in around 8 per 100,000 people each year. Compression of the brain and/or spinal cord by a meningioma can lead to symptoms such as headaches, seizures, vision loss, mental changes and weakness. They are mostly treated by surgical removal (resection), which might be combined with radiotherapy, especially if the location of the tumor is such that it is not entirely resectable. Radiation therapy alone can sometimes be used to treat small tumors.
Introduction
The term “meningioma” was coined by Dr. Harvey Cushing in 1922. Since that time, the understanding of meningioma has greatly improved and several subtypes have been identified. As of 2021, the World Health Organization (WHO) classification system changed to use of Arabic numbers for grading and specifying Central Nervous System (CNS) tumors as the 2021 version of WHO classification and recognizing meningioma as a single tumor type with 15 subtypes (ref). Meningiomas remain largely divided into three grades determined by histologic appearance. of The exception remains that grade 1 meningioma will be classified as grade 2 if brain invasion by the tumor is present. Most meningioma (80-85%) are benign tumors (grade 1), 15 to 18% are atypical (grade 2) and 1 to 3% are malignant (grade 3). High grade tumors can arise on their own (de novo) or result from the malignant progression of lower grade tumors.
Meningioma can occur at any age but tend to occur in older individuals; the median age at diagnosis is 65 years (meaning that half of diagnosed people will be over that age and the other half below). The potential symptoms of meningioma are variable and depend on the location of the tumor and the locations of the brain and spine that are compromised.
Parasagittal meningioma can lead to symptoms such as headaches, seizures, and limb weakness. Pressure inside the skull (intracranial pressure) might be increased and lead to swelling of the optic nerve (papilledema) and blurry vision. Other visual defects can also develop. Compression on the frontal lobe can lead to personality changes, decreased cognition, and lack of emotion and interest (apathy). Involvement of the cerebellum can lead to gait imbalance (ataxia), decreased coordination (dysmetria), and involuntary eye movements (nystagmus). Hearing loss can occur if the tumor is located at the junction between the cerebellum and a region of the brainstem known as the pons (cerebellopontine angle). A tumor located in the opening of the skull where the spinal cord connects with the brainstem (foramen magnum) can also lead to arm and leg weakness. Compression from a meningioma can also impair cerebrospinal fluid drainage and lead to accumulation of cerebrospinal fluid in the brain, a condition known as hydrocephalus (for more information on this disorder, choose “hydrocephalus” as your search term in the Rare Disease Database). About 10% of meningioma occur in the spine (spinal meningioma), most commonly in the thoracic portion. Symptoms associated with spinal cord lesions include difficulty walking, leg weakness and numbness, pain, and difficulty with urination and/or bowel movements.
As most meningioma are benign, survival rates of affected individuals are relatively high: more than 80% of patients survive more than 5 years, around 75% survive more than 10 years, and about 70% survive more than 15 years. Older age, male gender, poor baseline health and high grade tumors are associated with lower survival rates.
Lower grade meningioma that are completely removed surgically do not usually recur. However, some tumors cannot be removed completely due to their location and proximity to crucial structures. A rule of thumb for recurrence of an incompletely resected meningioma is that the rate of recurrence is 30, 60 and 90% at 5, 10 and 15 years, respectively. Higher grade tumors might recur even with apparent complete resection, most often within 2 or 3 years. Tumors that have already recurred have a higher chance of recurring again, usually within a shorter time interval. Metastases to the spine and other organs are rare in meningioma and are most commonly associated with grade 3 tumors.
As their name indicates, meningioma is derived from the meninges, which are membranes that cover the brain and spinal cords. More specifically, most meningioma originate from a type of cells within the meninges known as arachnoid cap cells, which are involved in the resorption of cerebrospinal fluid.
Although the exact reasons why meningioma occur in certain individuals is unknown in most cases, several molecular mechanisms are thought to be involved in the development of meningioma. Several genes are often changed (mutated) in meningioma cells, one of the most important being NF2. This gene produces merlin, a tumor suppressor protein that decreases (inhibits) the growth of cells that are in contact with each other. Meningioma cells have also been shown to express the survivin protein, which is an inhibitor of programmed cell death (apoptosis). Growth factors and growth factor receptors such as platelet-derived growth factor and HER2 also play a role in the development of some meningioma. Tumors overexpressing HER2 seem to be associated with a higher recurrence rate.
Meningioma shares other features that are characteristic of many types of tumors: they tend to generate numerous blood vessels that will allow an increased influx of nutrients that can facilitate growth. Vascular endothelial growth factor (VEGF) is involved in the development of new blood vessels (angiogenesis) and is frequently overexpressed by numerous tumors including meningioma. A feature more common in malignant meningioma is an increased ability to elongate telomeres due to mutations in the TERT gene. Telomeres are located at the end of chromosome and shorten with each cell division until they become too short for the cell to divide. They can be elongated by the enzyme telomerase, therefore giving an increased replication potential to cells and facilitating tumor growth. The TERT gene encodes a subunit of the telomerase enzyme.
Another recently identified poor prognosis genetic mutation is the homozygous loss of CDKN2A [Sievers 2020]. Patients with meningiomas harboring this homozygous deletion had a far short time to recurrence that those who did not.
Several meningioma harbor progesterone, estrogen, and androgen receptors, which indicates that hormones might potentially be involved in the growth of some meningioma. Other factors suggesting a role of sex hormones in meningioma is the fact that they are more common in women and that associated symptoms can increase during periods of progesterone excess, such as pregnancy. The role of sex hormones in the development and growth of meningioma is however not entirely understood.
In the United States, about 40% of primary brain tumors are meningiomas. In 2023, it is estimated that about 42,000 people will be diagnosed with meningioma. However, this is likely an underestimation, as autopsy data shows that up to 2.8% of individuals have a meningioma. Most of these tumors are too small to cause symptoms and will never grow enough to be clinically significant.
Meningioma most commonly occur in older individuals, the median age at diagnosis being 65 (meaning that half of diagnosed people will be over that age and the other half below). They rarely occur in children. Notably, they arise in association with syndromes such as neurofibromatosis type II (see the “related disorders” section for more details). They occur 2 to 3 times more commonly in adult women, but are equally common in boys and girls and in the case of malignant meningioma. Spinal meningioma occurs at a 9:1 female: male ratio. Meningioma is also slightly more common in black individuals. Another well-established risk factor is previous exposure to ionizing radiation, such as in the case of individuals who have previously been treated with radiotherapy to the head. Radiation-associated meningioma are more likely to be atypical or malignant and multiple. More often, they occur 15 or more years after exposure to radiation.
The diagnosis of meningioma is mostly based on a patient history and physical examination, medical imaging, and analysis of the cells composing the tumor. A patient that has signs and symptoms suggestive of a central nervous system lesion such as recent onset of seizures or neurological deficits (for more details, see the “Signs & Symptoms” section) will usually undergo brain and/or spine medical imaging with a computed tomography (CT) scan or magnetic resonance imaging (MRI). MRI is the imaging modality of choice for initial evaluation of brain tumors. Although the presence of a meningioma can be suspected with medical imaging due to their characteristic location, analysis of the cells of the tumor provides the most definitive diagnosis. Meningioma cells can be obtained by removing a piece of the tumor with a biopsy. However, meningiomas are usually removed surgically without a prior biopsy as this provides therapeutic in addition to diagnostic benefit. Once tumor cells are obtained, they can be analyzed under the microscope by a pathologist, who will confirm the diagnosis. A laboratory technique called immunohistochemistry can be used to stain meningioma cells to facilitate their identification.
Treatment & Management
The standard treatment for meningioma is complete removal (resection) of the tumor. This procedure is performed by a neurosurgeon; a physician specialized in the surgical treatment of diseases of the nervous system. To access the brain to resect the tumor, a part of the skull is removed (craniotomy) and put back in place after the surgery. If the tumor has a high blood supply that might complicate surgery, a technique called angiography might be used before surgery to block (embolize) the blood vessels that feed the tumor to facilitate its resection. Different surgical techniques can be used in the case of spinal meningiomas. Often, surgery alone will be sufficient. However, if the location of the tumor is such that it cannot be entirely resected due to proximity to crucial structures, radiation therapy can be used alone or in combination with surgery. Radiation oncologists are physicians specialized in the use of radiation therapy for the treatment of tumors and cancers. Radiation therapy involves the use of high-energy x-rays or other types or energy to destroy tumor cells. For meningioma, external-beam radiation therapy is most commonly used. Many types of machines can be used for external-beam radiation therapy, but the goal is the same in all cases: to target the tumor and expose it to multiple beams of radiation to stop it from growing while avoiding damage to healthy brain tissue as much as possible. Due to the high risk of recurrence, radiation therapy is often used intentionally after surgery in the case of many atypical meningiomas and routinely with all malignant meningioma, even if the tumor has been completely resected. Radiation therapy might be used alone if the tumor is not accessible by surgery. Chemotherapy and other drugs are not routinely used for the treatment of meningioma. With regards to supportive medications to treat side effects of meningiomas, anti-seizure medication (anticonvulsants) are often used if the affected individual experiences seizures. After treatment, patients might have to undergo rehabilitation to recover functions affected by the tumor or its treatment. Rehabilitation teams comprise many health professionals, including physicians, physiotherapists, occupational therapists, and nurses.
There are several new and exciting drugs being developed and investigated to treat meningiomas. These include using drugs that are specifically targeted to a mutation found in some meningiomas or use of immunotherapy that enhances the immune system to fight the meningioma. . Temozolomide is one of the few chemotherapy agents that has been investigated with possible minor activity. As some meningioma express progesterone, estrogen, and androgen receptors, blockers of those receptors are a potential therapeutic target, but most studies with these medications have not shown to be effective to date. Meningioma tends to be fed by numerous blood vessels. Bevacizumab is a medication that blocks vascular endothelial growth factor (VEGF), which is a blood vessel growth factor, and could therefore show potential in the treatment of meningioma. Again, studies with bevacizumab suggest minimal response and possibly greatest clinical benefit in reducing symptoms secondary to decreasing associated tissue swelling. Other growth factors which fall within the targets for novel drug therapies can be used.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/for-patients-and-families/information-resources/info-clinical-trials-and-research-studies/
For information about clinical trials sponsored by private sources, contact:
https://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
TEXTBOOKS
Perry A. Meningiomas, Editor(s): Arie Perry, Daniel J. Brat, Practical Surgical Neuropathology: A Diagnostic Approach (Second Edition),Elsevier,2018,Pages 259-298, ISBN 9780323449410, https://doi.org/10.1016/B978-0-323-44941-0.00013-8.
(https://www.sciencedirect.com/science/article/pii/B9780323449410000138)
JOURNAL ARTICLES
Bhala S, Stewart DR, Kennerley V, Petkov VI, Rosenberg PS, Best AF. Incidence of Benign Meningiomas in the United States: Current and Future Trends. JNCI Cancer Spectr. 2021;5(3):pkab035. Published 2021 Apr 8. doi:10.1093/jncics/pkab035
Sievers P, Hielscher T, Schrimpf D, et al. CDKN2A/B homozygous deletion is associated with early recurrence in meningiomas. Acta Neuropathol. 2020;140(3):409-413. doi:10.1007/s00401-020-02188-w
Benz LS, Wrensch MR, Schildkraut JM, et al. Quality of life after surgery for intracranial meningioma. Cancer 2018;124:161-6.
Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 2016;131:803-20.
Sahm F, Schrimpf D, Olar A, et al. TERT Promoter Mutations and Risk of Recurrence in Meningioma. J Natl Cancer Inst 2016;108.
Yuzawa S, Nishihara H, Tanaka S. Genetic landscape of meningioma. Brain Tumor Pathol 2016;33:237-47.
Riad H, Knafo S, Segnarbieux F, Lonjon N. Spinal meningiomas: surgical outcome and literature review. Neurochirurgie 2013;59:30-4.
van Alkemade H, de Leau M, Dieleman EM, et al. Impaired survival and long-term neurological problems in benign meningioma. Neuro Oncol 2012;14:658-66.
Curto M, McClatchey AI. Nf2/Merlin: a coordinator of receptor signalling and intercellular contact. Br J Cancer 2008;98:256-62.
Marosi C, Hassler M, Roessler K, et al. Meningioma. Crit Rev Oncol Hematol 2008;67:153-71.
Simon M, Bostrom JP, Hartmann C. Molecular genetics of meningiomas: from basic research to potential clinical applications. Neurosurgery 2007;60:787-98; discussion -98.
Whittle IR, Smith C, Navoo P, Collie D. Meningiomas. Lancet 2004;363:1535-43.
INTERNET
Meningioma Statistics. Cancer.Net. 2023. https://www.cancer.net/cancer-types/meningioma/statistics# Accessed Sept 6, 2023.
Haddad G., Turkmani A., Meningioma, Medscape. Last Updated Oct 5, 2022. https://emedicine.medscape.com/article/1156552-overview Accessed May 23, 2023.
Meningioma: Diagnosis, American Society of Clinical Oncology. Last updated: 12/2021. https://www.cancer.net/cancer-types/meningioma/diagnosis Accessed May 23, 2023.
Meningioma: Types of Treatment, American Society of Clinical Oncology. Meningioma: Types of Treatment | Cancer.Net Last updated: 11/2018. 21 Accessed May 23, 2023.
Park PK, Epidemiology, clinical features, and diagnosis of meningioma, UpToDate. Last updated: Jan 24, 2023. https://www.uptodate.com/contents/epidemiology-pathology-clinical-features-and-diagnosis-of-meningioma Accessed May 23. 2023.
Park PK, Management of known or presumed benign (WHO grade I) meningioma, UpToDate. Last updated: Jan 24, 2023. https://www.uptodate.com/contents/management-of-known-or-presumed-benign-who-grade-i-meningioma Accessed May 23. 2023.
Park PK, Shih HA. Patient education: Meningioma (Beyond the Basics), UpToDate. Last updated: Sep 02, 2022. https://www.uptodate.com/contents/meningioma-beyond-the-basics Accessed May 23, 2023.
Shih HA, Park PK, Management of atypical and malignant (WHO grade II and III) meningioma, UpToDate. Last updated: Jan 03, 2023. https://www.uptodate.com/contents/management-of-atypical-and-malignant-who-grade-ii-and-iii-meningioma Accessed May 23, 2023.
Wen PY, Systemic treatment of recurrent meningioma, UpToDate. Last updated: Jan 23, 2023. https://www.uptodate.com/contents/systemic-treatment-of-recurrent-meningioma Accessed May 23, 2023.
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